The main objective of this project is to characterize the protective antigens and immune responses induced in human and non-human primates by immunization with P. vivax irradiated sporozoites (irr-spz). This will be accomplished by the following: 1. Establish a model for malaria protection by immunizing with P. vivax irr-spz in monkeys and then in humans, 2. Identify the protective immune mechanisms induced by P. vivax irr-spz immunization, 3. Identify and characterize P. vivax non-CSP antigens involved in protection. We propose to infect A. albimanus with P. vivax in order to produce infective sporozoites. Plasmodium vivax infected mosquitoes will be used to determine the optimal number of injections or bites required to induce protection in primates and humans respectively. Successful development of this model will allow us to compare the baseline immune responses of monkeys and humans exposed to non-irradiated P. vivax sporozoites with those exposed to irradiated P. vivax sporozoites, and thereby broadly identify the protective immune mechanisms. Analyses will then concentrated on characterizing the protective mechanisms to specifically identify and characterize antibody responses, Th and CTL epitopes, cytokines profiles and other soluble products from the immune response that are responsible for the protection. By the use of reagents obtained from protected subjects (see/cells). A critical component of these analyses is to identify and characterize additional parasite antigens involved in protection. Particular emphasis will be put on discovering and cloning P. vivax homologues of the P. falciparum LSA-1 and LSA-3 antigen, as well as novel antigens with may have homology to undiscovered P. falciparum antigens. We expect that these studies will lead to the identification of sub-unit antigens for a pre-erythrocytic stage P. vivax malaria vaccine, which may include novel malaria antigen homologous useful for the development of a P.falciparum vaccine.